This investigation undertakes to determine which mechanisms underlie variation in antibiotic-resistance plasmids. Some of these are due to recombination between plasmids carried by a single bacterial host, (1) substitutive interchange of sequences; (2) insertion of DNA sequences either randomly or site-specific (which may result in gene inactivations) and (3) deletion of base sequences. Two useful examples for these studies include a recombinant F-lac-tet plasmid and R46. The CCC DNA is being extracted from variants of these plasmids, and genetic characterization and biophysical properties studied to correlate the drug resistance properties of the plasmids with molecular fine structure. The experiments will compare normal hosts with mutants defective in DNA repair functions to find which regulate these molecular events as well as similar plasmid-coded genes. Some of the relevant DNA molecules have been extracted, and this work is proceeding. We hope to determine endonuclease R1 restriction sites by gel electrophoresis, to measure contour lengths, and to examine heteroduplexes between wild-type and variant plasmid molecules.